{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:09:22Z","timestamp":1789398562081,"version":"build-2803163510"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T00:00:00Z","timestamp":1709337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T00:00:00Z","timestamp":1709337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Inhibition of the adenosine 2A receptor (A<jats:sub>2A<\/jats:sub>R) diminishes the immunosuppressive effects of adenosine and may complement immune-targeting drugs. This phase 2 study evaluated the A<jats:sub>2A<\/jats:sub>R antagonist AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients with histologically\/cytologically confirmed disease progressing within 6\u00a0months on\u2009\u2265\u20092 therapy lines were randomly assigned to either Module 1 (AZD4635\u2009+\u2009durvalumab) or Module 2 (AZD4635\u2009+\u2009oleclumab). Primary endpoints were objective response rate per RECIST v1.1 and prostate-specific antigen (PSA) response rate. Secondary endpoints included radiological progression-free survival (rPFS), overall survival, safety, and pharmacokinetics.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Fifty-nine patients were treated (Module 1, n\u2009=\u200929; Module 2, n\u2009=\u200930). Median number of prior therapies was 4. One confirmed complete response by RECIST (Module 1) and 2 confirmed PSA responses (1 per module) were observed. The most frequent adverse events (AEs) possibly related to AZD4635 were nausea (37.9%), fatigue (20.7%), and decreased appetite (17.2%) in Module 1; nausea (50%), fatigue (30%), and vomiting (23.3%) in Module 2. No dose-limiting toxicities or treatment-related serious AEs were observed. In Module 1, AZD4635 geometric mean trough concentration was 124.9\u00a0ng\/mL (geometric CV% 69.84; n\u2009=\u200922); exposures were similar in Module 2. In Modules 1 and 2, median (95% CI) rPFS was 2.3 (1.6\u2009\u20133.8) and 1.5 (1.3\u2013\u20094.0)\u00a0months, respectively. Median PFS was 1.7 versus 2.3\u00a0months for patients with high versus low blood-based adenosine signature.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In this heavily pretreated population, AZD4635 with durvalumab or oleclumab demonstrated minimal antitumor activity with a manageable safety profile. Clinical Trial.gov identifier: NCT04089553.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00262-024-03640-6","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T13:01:28Z","timestamp":1709384488000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A phase 2 study of AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer"],"prefix":"10.1007","volume":"73","author":[{"given":"Gerald S.","family":"Falchook","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Reeves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Gandhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Spigel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Arrowsmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Karlix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayle","family":"Pouliot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen M.","family":"Hattersley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T.","family":"Gangl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth D.","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna L.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavickumar","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerson","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"issue":"3","key":"3640_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Falchook: Royalties (self): Wolters Kluwer (2014-present); Advisory role (to institution): Fujifilm (2018), Silicon (2020, 2021), Navire (2021), Turning Point (2021), Predicine (2021), Inspirna (2021), Regeneron (2021) Advisory role (self): EMD Serono (2010, 2011); Speakers honorarium for CME: Total Health Conferencing (2019), Rocky Mountain Oncology Society (2020); Travel (self, for work or research related to institution): Bristol Myers Squibb (2015), EMD Serono (2011, 2012, 2013), Fujifilm (2018), Millennium (2013), Sarah Cannon Research Institute Research funding [to institution, for any trial for which I have been the PI (ever) or subinvestigator (minimum last 4 years): 3-V Biosciences, Abbisko, AbbVie, ABL Bio ADC Therapeutics, Accutar, Aileron, American Society of Clinical Oncology, Amgen, ARMO\/Eli Lilly, Artios, AstraZeneca, BeiGene, Bioatla, Bioinvent, Biothera, Bicycle, Boehringer Ingelheim, Celldex, Celgene, Ciclomed, Curegenix, Curis, Cyteir, Daiichi, DelMar, eFFECTOR, Eli Lilly, EMD Serono, Epizyme, Erasca, Exelixis, Freenome, Fujifilm, Genmab, GlaxoSmithKline, Hutchison MediPharma, IGM Biosciences, Ignyta, ImmunoGen\/MacroGenics, Incyte, Jacobio, Jounce, Kolltan, Loxo\/Bayer, MedImmune, Millennium, Merck, miRNA Therapeutics, Molecular Templates, National Institutes of Health, Navire, NiKang, Novartis, OncoMed, Oncorus, Oncothyreon, Poseida, Precision Oncology, Prelude, PureTech, Pyramid, RasCal, Regeneron, Relay, Rgenix, Ribon, Samumed, Sapience, Silicon, Simcha, Sirnaomics, Strategia, Syndax, Synthorx\/Sanofi, Taiho, Takeda, Tarveda, Teneobio, Tesaro, Tocagen, Turning Point, U.T. MD Anderson Cancer Center, Vegenics, Xencor. James Reeves: None. Sunil Gandhi: None. David Spigel: None. Edward Arrowsmith: Tennessee Oncology Stock. Other Ownership Interests: One Oncology Research Funding: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Calistoga Pharmaceuticals, Celgene, Cephalon, Chorus, Cougar Biotechnology, Eisai, EMD Serono, Evelo Biosciences, Exelixis, Genentech, Gilead Sciences, Incyte, Merck Sharp & Dohme, Millennium, Modra Pharmaceuticals, Novartis, Oncogenex, Onyx, Peloton Therapeutics, Pfizer, Sarah Cannon Research Institute, Takeda, Clovis Oncology, Lilly, Infinity Pharmaceuticals, Janssen Research & Development Travel, Accommodations, Expenses: Flatiron Health, OneOncology, Sarah Cannon Research Institute. Other Relationship: Sarah Cannon Research Institute. Daniel J. George: Consultant for Astellas, AstraZeneca, Bayer H\/C Pharmaceuticals, BMS, Constellation Pharmaceuticals, Exelixis, Inc, Flatiron, IdeoOncology (formerly Nexus), Janssen Pharmaceuticals, Merck Sharp & Dohme, Michael J Hennessey Associates, Myovant Sciences, Inc, Physician Education Resource LLC, Pfizer, PlatformQ, Propella TX\u2013Consultant (formerly Vizuri), RevHealth, LLC, Sanofi, Seattle Genetics, WebMD, and Xcures. Speaker\u2019s honorarium for Bayer H\/C Pharmaceuticals, EMD Serono, Exelixis, Inc, Ipsen, Michael J Hennessey Associates, Pfizer, Sanofi, UroGPO, and UroToday. Advisory Role (self and institution) for Astellas, AstraZeneca, Capio Biosciences, and Modra Pharmaceuticals B.V. Travel accommodations from Bayer H\/C Pharmaceuticals, Exelixis, Inc, Sanofi, and UroToday. Research funding (self and institution) from AstraZeneca, Astellas, BMS, Calithera (institution only), Exelixis, Inc, Janssen Pharmaceuticals, Novartis (institution only), Pfizer, and Sanofi. Steering Committee for Astrazeneca, Bayer H\/C Pharmaceuticals, BMS, Leidos Biomedical Research Inc, Nektar Therapeutics, and Pfizer. Sr Editor for American Association for Cancer Research and Co\u2010Editor\u2010in\u2010Chief for Millennium Medical Publishing, Clinical Advances in Hematology & Oncology. Independent contractor for Axess Oncology. Independent Data Monitoring Committee for Janssen Pharmaceuticals. Janet Karlix: None. Gayle Pouliot: Employee of AstraZeneca and may own stock or stock options. Maureen M. Hattersley: Employee of AstraZeneca and may own stock or stock options. Eric T Gangl: Employee of AstraZeneca and may own stock or stock options. Gareth D James: Contractor for AstraZeneca. Jeff Thompson: Employee of AstraZeneca and may own stock or stock options. Deanna Russell: Employee of AstraZeneca and may own stock or stock options. Bhavickumar Patel: Employee of AstraZeneca and may own stock or stock options. Rakesh Kumar: Employee of AstraZeneca and may own stock or stock options. Emerson Lim: None.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted in accordance with the protocol and consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable ICH Good Clinical Practice guidelines, and applicable laws and regulations (Independent Ethics Committee\/Institutional Review Board).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all patients prior to enrollment into the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Not applicable; no personal or identifying data for patients have been included in this article.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"72"}}